September 23, 2013. Delusions might arise from garbled signals in the sensory cortex, but their maintenance may rely on top-down shaping by frontal cortex regions encoding beliefs, according to a study published August 21 in the Journal of Neuroscience. Led by Philipp Sterzer of Charité Universitätsmedizin Berlin, Germany, the study examined how the visual perceptions of healthy study participants were molded by their beliefs. The study found that perceptions were more malleable in people prone to subclinical delusions, both in the absence and presence of a belief that biased their ideas about what they should be seeing. The results may lead to insights into the debilitating delusions of schizophrenia.

Despite being bombarded by noisy sensory information, we manage to perceive the world as a stable place. That’s because the brain constantly interprets incoming sensory signals based on previous experience, and any mismatches between what is received and what was expected updates a person’s internal model of the world. Problems with this interpretation process could create abnormal perceptions, which in turn could drive delusions that try to make sense of the seemingly strange events (Corlett et al., 2010). This could stem from a process of aberrant salience in which the brain inaccurately flags innocuous sensory events as important, perhaps through haphazard dopamine signaling (Kapur, 2003) or sluggish brain networks (see SRF related news story). An irrelevant sensory event could then come to hold great meaning for someone and provide grist for delusions.

Consistent with this view, the new study finds evidence for pronounced perceptual instability in people prone to delusions. But it also addresses how delusions can remain so fixed, despite evidence to the contrary. The researchers found that a top-down process involving the orbitofrontal cortex (OFC) can shape visual perception, and the power the OFC had over visual cortex correlated with delusion proneness. This suggests a vicious cycle: Perceptual anomalies drive delusion formation, which in turn shape perception to fit with a warped internal model of the world.

Spinning spheres
First author Katharina Schmack and colleagues presented 105 healthy people with moving dot stimuli on a screen that suggested a spinning sphere. The participants were asked to report the direction of the sphere rotation. In the first experiment, the researchers presented different stimuli to each eye, so that one eye saw a sphere rotating in one direction, and the other eye saw the sphere rotating in the opposite direction. Despite this ambiguity, people will glimpse a stable percept, with the sphere appearing to move in one direction for awhile, then in the other. A stable percept is thought to result when the brain begins to infer the direction of motion, based on previous experience with the stimulus—a process known to involve early stages of sensory processing in visual cortex.

The researchers found that the stability of reported rightward or leftward rotation varied according to a person’s delusional conviction score, as measured by a delusion inventory questionnaire (r = -0.26, p = 0.004). This means that people for whom the spheres alternated quickly between rightward and leftward rotation tended to be more convinced of delusion-like beliefs than those for whom the sphere rotation appeared more stable. Eye movements measured in 66 of the participants did not explain the differences in perceptual stability.

Next, the researchers introduced a false belief to bias perception. They gave participants glasses to wear while viewing the sphere stimuli, telling them that they were polarizing filters that would bias their perception in one direction. In reality, the glasses were transparent, but the sphere stimuli were changed to produce coherent rotation in one direction. In the initial learning phase, people reported longer bouts of coherent rotation in one direction. In the following test phase, however, the participants viewed the ambiguous sphere stimuli through the glasses. They reported longer bouts of coherent rotation compared to what they had reported during the baseline viewing of ambiguous stimuli without the glasses. This suggests that a false belief shaped perception of the ambiguous stimuli, and those people who were more delusion prone tended to show a stronger influence by the false belief (r = 0.26, p = 0.004). Again, eye movements did not explain the differences.

From on high
But was perception really shaped by the fake glasses, or did the participants just make up their minds more readily? The study argues for the former, as functional magnetic resonance imaging showed neural correlates for the spinning sphere in early occipital visual areas and the motion-sensitive area MT. A new group of 20 participants were scanned while they did the fake glasses experiment, and they, too, showed the belief-induced bias on rotation direction. Using multi-voxel pattern analysis (MVPA) techniques to locate parts of the brain whose activity best matched the reported percepts (i.e., rightward or leftward rotation), the researchers found a pattern of activity associated with reported rotation direction during the ambiguous baseline phase. This same pattern was linked to the reported rotation directions during the false-belief phase, which suggests that perception was actually shaped.

To get a sense for the circuitry involved in the belief-induced shaping of perception, the researchers followed the activity in the OFC, a region already on the radar for mediating placebo effects on sensory signals (Wager et al., 2004). Indeed, they found that the left OFC was recruited only during the false belief portion of the experiment; activation in other regions was not observed. What’s more, functional connectivity between the OFC and the visual cortex—as measured by co-activation of these two regions—was increased during the experiment, but only during the ambiguous stimuli, when the need for perceptual inference was higher. The researchers also report that the strength of this coupling was greater for people who were more delusion prone (r = 0.44, p = 0.035).

Together, the results suggest a self-reinforcing interaction between perceptions and beliefs: Unstable perceptions create an odd belief, and this belief then shapes perception to fit with it. A recent study using ketamine to model mild psychotic symptoms also suggests a link between delusion creation and maintenance (Corlett et al., 2013). This may help explain the enduring nature of delusions in schizophrenia, and future research will have to examine these processes in the far-fetched delusions of psychosis.—Michele Solis.